rhyncophylline and Inflammation

Atherosclerosis is a chronic inflammatory disease of arterial wall, which is closely related to inflammatory reaction. In this study, the anti-inflammatory effect of isorhynchophylline was studied by NF- κB / NLRP3 pathway.. (1) ApoE. (1) the expression of NLRP3, NF- κB, IL-18 and Caspase-1 in aorta of model group was higher than that of control group, and plaque formation was obvious. (2) the expressions of NLRP3, NF- κB, IL-18 and Caspase-1 in HUVECs and RAW264.7 model groups were higher than those in control group, while isorhynchophylline decreased their expression and enhanced cell migration ability.. Isorhynchophylline can reduce the inflammatory reaction induced by lipopolysaccharide and promote the ability of cell migration.

Topics: Animals; Atherosclerosis; Caspases; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Interleukin-18; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction

Alzheimer's disease (AD), the most common neurodegenerative disease, has limited treatment options. As such, extensive studies have been conducted to identify novel therapeutic approaches. We previously reported that rhynchophylline (Rhy), a small molecule EphA4 inhibitor, rescues impaired hippocampal synaptic plasticity and cognitive dysfunctions in APP/PS1 mice, an AD transgenic mouse model. To assess whether Rhy can be developed as an alternative treatment for AD, it is important to examine its pharmacokinetics and effects on other disease-associated pathologies. Here, we show that Rhy ameliorates amyloid plaque burden and reduces inflammation in APP/PS1 mice. Transcriptome analysis revealed that Rhy regulates various molecular pathways in APP/PS1 mouse brains associated with amyloid metabolism and inflammation, specifically the ubiquitin proteasome system, angiogenesis, and microglial functional states. These results show that Rhy, which is blood-brain barrier permeable, is beneficial to amyloid pathology and regulates multiple molecular pathways.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Disease Models, Animal; Inflammation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurodegenerative Diseases; Oxindoles; Plaque, Amyloid; Presenilin-1

Hyperplasia of airway smooth muscle cells (ASMCs) is key to the progression of asthma. Isorhynchophylline (IRN) derived from Uncaria rhynchophylla can inhibit the proliferation of AMSCs. The major purpose of the current study was to assess the effect of IRN on the asthma symptoms was assessed both in vitro and in vivo, and the associated mechanism of the effect was also explored by focusing on the function of miR-200a. Asthma model was induced using ovalbumin (OVA) method and AMSC hyperplasia model was induced using TGF-β1. The effect of IRN on allergic asthma mice and the effect of IRN on the proliferation of ASMCs were investigated as well, and the changes in miR-200a level and FOXC1/NF-κB pathway were detected. The administration of IRN attenuated the eosinophils recruitment in BALF, reduced collagen deposition in lung tissues, and suppressed production of IgE and pro-inflammation cytokines. IRN also inhibited the proliferation and induced the apoptosis of ASMCs. Moreover, the administration of IRN increased the level of miR-200a while inhibited the activation of FOXC1/NF-κB pathway. However, after the inhibition of miR-200a level, the function of IRN on ASMCs was impaired. Collectively, it was demonstrated that the effect of IRN on asthma relied on the up-regulation of miR-200a, which then deactivated FOXC1/NF-κB pathway.

Topics: Animals; Asthma; Cell Proliferation; Collagen; Disease Models, Animal; Eosinophils; Forkhead Transcription Factors; Gene Expression Regulation; Hyperplasia; Immunoglobulin E; Inflammation; Lung; Mice, Inbred BALB C; MicroRNAs; Myocytes, Smooth Muscle; NF-kappa B; Oxindoles; Signal Transduction

Excessive activation of microglial cells has been implicated in various types of neuroinflammation. Suppression of microglial activation would have therapeutic benefits, leading to the alleviation of the progression of neurodegeneration. In this study, the inhibitory effects of rhynchophylline (RIN), a tetracyclic oxindole alkaloid component isolated from Uncaria rhynchophylla (Miq.) Jacks., on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated microglia. The results showed that RIN markedly reduced the production of nitric oxide (NO), prostaglandins E(2) (PGE(2) ), monocyte chemoattractant protein (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in LPS-activated microglia. The mRNA expression levels of iNOS and COX-2 were also depressed by RIN in a concentration-dependent manner. Further studies revealed that RIN blocked IκBα phosphorylation and degradation, inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs). In summary, these data suggest that RIN suppresses inflammatory responses of microglia and may act as a potential therapeutic agent for various neurodegenerative diseases involving neuroinflammation.

Topics: Animals; Cell Survival; Cells, Cultured; Chemokine CCL2; Cyclooxygenase 2; Dinoprostone; Down-Regulation; I-kappa B Proteins; Indole Alkaloids; Inflammation; Inflammation Mediators; Interleukin-1beta; Lipopolysaccharides; MAP Kinase Signaling System; Microglia; Mitogen-Activated Protein Kinases; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Nitric Oxide Synthase Type II; Oxindoles; Phosphorylation; Rats; Signal Transduction; Tumor Necrosis Factor-alpha